Three physiologic roles in normal lung function have been proposed for the nonciliated epithelial (Clara) cells lining small conducting pulmonary airways (bronchioles): 1) secretion of airway lining material; 2) metabolism of chemical toxins and carcinogens; and 3) progenitor cell for bronchiolar epithelium. The goal of this line of investigation is to clarify these separate functions of the Clara cell with emphasis on its role in detoxification and carcinogen metabolism, and on the interrelationship between these various functions. Work is progressing along the following lines: First, a comparative study of the cellular characteristics of this cell type in the lungs of twelve species of mammals, including man, has been undertaken to define the Clara cell as a lung cell type and to identify species that could serve as useful models for subsequent investigations. Second, the detoxification function will be characterized in terms of the cellular response during exposure, and the time course of events during the response and subsequent recovery phase. Third, the actual site of the cytochrome P-450's among the various lung cell types and their intracellular distribution will be determined using the unlabelled antibody immunoperoxidase technique.